Lactate-driven Type I Collagen Deposition Facilitates Cancer Stem Cell-like Phenotype of Head and Neck Squamous Cell Carcinoma

Overview

Journal iScience

Publisher Cell Press

Date 2024 Mar 19

PMID 38500829

Authors

Yunqing Sun

Yang Chen

Hui Zhao

Jingjing Wang

Yuantong Liu

Junqiang Bai

Chuanyu Hu

Zhengjun Shang

Affiliations

Soon will be listed here.

Abstract

Lactate is known to play a crucial role in the progression of malignancies. However, its mechanism in regulating the malignant phenotype of head and neck squamous cell carcinoma (HNSCC) remains unclear. This study found that lactate increases cancer stem cell (CSC) characteristics of HNSCC by influencing the deposition of type I collagen (Col I). Lactate promotes Col I deposition through two distinct pathways. One is to convert lactate to pyruvate, a substrate for Col I hydroxylation. The other is the activation of HIF1-α and P4HA1, the latter being a rate-limiting enzyme for Col I synthesis. Inhibition of these two pathways effectively counteracts lactate-induced enhanced cell stemness. Further studies revealed that Col I affects CSC properties by regulating cell cycle dynamics. In conclusion, our research proposes that lactate-driven Col I deposition is essential for the acquisition of CSC properties, and lactate-centric Col I deposition may be an effective target for CSCs.

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